Comparison of Standard Dose Alectinib to Alectinib in Adjusted Dose Based on Alectinib Bloodlevels

Официальное название

Standard Dosed Alectinib Versus Therapeutic Drug Monitoring Guided Alectinib Dosing

Обзор

The ADAPT ALEC randomized controlled trial (RCT) is performed in patients with Anaplastic Lymphoma Kinase (ALK) positive non-small cell lung cancer (NSCLC). The RCT will compare the use of Therapeutic Drug Monitoring (TDM) and dose increases if alectinib 35 ng/Ml (arm A) with standard of care (arm B).

Подробное описание

The ADAPT ALEC trial is a phase IV, RCT in patients with ALK positive NSCLC treated with alectinib. A longer median progression free survival (mPFS) is expected in patients treated with standard dose alectinib when minimum plasma concentrations (Cmin) of alectinib exceed 435 ng/mL. The ADAPT ALEC trial will investigate whether using therapeutic drug monitoring (TDM) and increasing the dose of alectinib in patients with Cmin \<435 ng/mL, will raise the mPFS. We will compare mPFS in the subgroup of patients with an alectinib Cmin \<435 ng/mL using TDM and dose increases (arm A) to fixed dosing/standard of care (arm B).

Вмешательства

• Препарат Alectinib
  In case of an alectinib plasmaconcentration Cmin \<435 ng/mL, determined by TDM, and manageable toxicity, the alectinib dose will be increased with 150mg BID up to a maximum of 900mg BID. In case of unacceptable toxicity (i.e. unbearable or persistent grade 2 toxicity and grade 3/4 toxicity), the alectinib dose can be reduced by 150mg BID.

Первичные конечные точки

• Median progression free survival (mPFS) [Срок оценки: mPFS will be assessed through study completion, after 12 months of follow-up.]

Вторичные конечные точки (10)

• Succesfull Therapeutic Drug monitoring [Срок оценки: 4 to 6 weeks after dose adjustment based on TDM]
• Overall response rate (ORR) [Срок оценки: Response will be assessed every 2-3 months. ORR will be determined after total study completion and 12 months of follow-up]
• Median overall survival [Срок оценки: Through total study completion, after 12 months of follow-up]
• Intracranial PFS [Срок оценки: Progressive disease will be assessed once every 2-3 months. Intracranial PFS will be assessed through total study completion, after 12 months of follow-up]
• Patient adherence to alectinib treatment [Срок оценки: Through study completion, an average of 2 years]
• Number of adverse events (AE) related to plasma concentration and dose increases [Срок оценки: Through total study completion, after 12 months of follow-up]
• European Organization for Research and Treatment of Cancer 30-item core quality of life questionnaire (EORTC QLQ-C30) and the the Quality of Life Questionnaire-Lung Cancer 13 (EORTC QLQ-LC-13) module [Срок оценки: Questionnaires will be filled in at baseline and every 3 months thereafter through study completion, an average of 2 years.]
• European Quality of Life Five Dimensions with five levels (EQ-5D-5L) questionnaire [Срок оценки: Questionnaire will be filled in at baseline and every 3 months thereafter through study completion, an average of 2 years.]
• Incremental cost-effectiveness ratio (ICER) [Срок оценки: Through total study completion, after 12 months of follow-up]
• Alectinib M4 protein [Срок оценки: Through total study completion, after 12 months of follow-up]

Критерии участия

Критерии включения

• Patients with locally advanced or metastatic NSCLC (stage IIIB to stage IV by AJCC 8th)
• ECOG performance status 0-4
• Histologically or cytology confirmed NSCLC
• Documented ALK rearrangement based on an EMA approved test
• Patients can either be chemotherapy-naïve or have received one line of platinum-based chemotherapy
• Patients with brain or leptomeningeal metastases are allowed on the study if the lesions are asymptomatic without neurological signs and clinically stable for at least 2 weeks without steroid treatment. Patients who do not meet these criteria are not eligible for the study
• Measurable disease (by RECIST criteria version 1.1) prior to the first dose of study treatment
• Signed writte Institutional Review Board (IRB)/Ethical Committee (EC) approved informed consent form, prior to performing any study-related procedures
• Observational other studies are allwoed for patients included in this study
• Local radiotherapy is allowed for pain

Критерии исключения

• Any significant concomitant disease determined by the investigator to be potentially aggravated by the investigational drug
• Consumption of agents which modulate CYP3A4 or agents with potential QT prolonging effects within 14 days prior to admission and during the study (see concomitant medication restrictions)
• Any clinically significant concomitant disease or condition that could interfere with, or for which the treatment might interfere with, the conduct of the study, or absorption of oral medications, or that would, in the opinion of the Principal Investigator, pose an unacceptable risk to the subject in this study.
• Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol requirements and/or follow-up procedures; those conditions should be discussed with the patient before trial entry.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Нидерланды · 7 центров

• Radboud University Medical Center — Nijmegen
• Maastricht University Medical Center + — Maastricht
• The Netherlands Cancer Institute — Amsterdam
• Amsterdam University Medical Center — Amsterdam
• Leiden University Medical Center — Leiden
• Erasmus Medical Center — Rotterdam
• University Medical Center Groningen — Groningen

Франция · 1 центр

• Gustave Roussy — Villejuif

Публикации

• Meertens M, Muntinghe-Wagenaar MB, Sikkema BJ, Lopez-Yurda M, Retel VP, Paats MS, Ter Heine R, Schuuring E, Timens W, Touw DJ, van Boven JFM, de Langen AJ, Hashemi SMS, Hendriks LEL, Croes S, van den Heuvel MM, Dingemans AC, Mathijssen RHJ, Smit EF, Huitema ADR, Steeghs N, van der Wekken AJ. Therapeutic drug monitoring guided dosing versus standard dosing of alectinib in advanced ALK positive non- PMID 36969063

Идентификаторы

NCT: NCT05525338 · 202000251 · 2020-001737-13 · NL9411

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗